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Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer caused by CDH1 mutation. HDGC causes multiple signet ring cell carcinomas (SRCCs) throughout the stomach. Few reports exist on the endoscopic findings during screening endoscopy, leading to the diagnosis of HDGC in its early stages. Recently, a new image-enhancement endoscopy technique, texture and color enhancement imaging (TXI), has been developed to improve the visibility of early gastric cancer. To the best of our knowledge, the use of TXI leading to HDGC diagnosis has not been reported. In this report, TXI contributed to the diagnosis of HDGC, and the patient was treated with total gastrectomy. A 27-year-old woman with a family history of gastric cancer underwent esophagogastroduodenoscopy, which revealed two pale lesions in the lower body of the stomach. Histological examination of the biopsy specimen revealed SRCC and the patient was referred to our hospital for treatment. Multiple lesions were found in the lower body using TXI, and a targeted biopsy confirmed other SRCCs. We suspected her disease to be HDGC, and the patient underwent a total gastrectomy. Histopathology showed multiple SRCCs (>60), but no lymph node metastases. Genetic testing revealed CDH1 mutations. The final pathological stage of the tumor was pT1a(m) N0M0 Stage I. TXI may be helpful in detecting multiple SRCCs in patients with HDGC. Endoscopists should be aware of HDGC, and careful investigation of the entire stomach is required for patients with diffuse-type gastric cancer before treatment., Competing Interests: All authors had full access to the data and had the final responsibility for the decision to submit for publication. No benefits in any form have been received or will be received from any commercial party directly or indirectly related to the subject of this study. Author Kazuki Sumiyama is the DEN Open's Deputy Editor‐in‐Chief., (© 2025 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: We aimed to develop a chemoimmunotherapy regimen consisting of a novel Wilms' tumor 1 (WT1) peptide-pulsed dendritic cell (WT1-DC) vaccine and multiagent chemotherapy and to investigate the safety, clinical outcomes, and WT1-specific immune responses of patients with unresectable advanced pancreatic ductal adenocarcinoma (UR-PDAC) who received this treatment., Methods: Patients with UR-PDAC with stage III disease (locally advanced (LA-PDAC; n=6)), stage IV disease (metastatic (M-PDAC; n=3)), or recurrent disease after surgery (n=1) were enrolled in this phase I study. The patients received one cycle of nab-paclitaxel plus gemcitabine alone followed by 15 doses of the WT1-DC vaccine independent of chemotherapy. The novel WT1 peptide cocktail was composed of a multifunctional helper peptide specific for major histocompatibility complex class II, human leukocyte antigen (HLA)-A*02:01, or HLA-A*02:06 and a killer peptide specific for HLA-A*24:02., Results: The chemoimmunotherapy regimen was well tolerated. In the nine patients for whom a prognostic analysis was feasible, the clinical outcomes of long-term WT1 peptide-specific delayed-type hypersensitivity (WT1-DTH)-positive patients (n=4) were significantly superior to those of short-term WT1-DTH-positive patients (n=5). During chemoimmunotherapy, eight patients were deemed eligible for conversion surgery and underwent R0 resection (four patients with LA-PDAC, one patient with M-PDAC, and one recurrence) or R1 resection (one patient with M-PDAC), and one patient with LA-PDAC was determined to be unresectable. Long-term WT1-DTH positivity was observed in three of the four patients with R0-resected LA-PDAC. These three patients exhibited notable infiltration of T cells and programmed cell death protein-1+ cells within the pancreatic tumor microenvironment (TME). All patients with long-term WT1-DTH positivity were alive for at least 4.5 years after starting therapy. In patients with long-term WT1-DTH positivity, the percentage of WT1-specific circulating CD4+ or CD8+ T cells that produced IFN-γ or TNF-α was significantly greater than that in patients with short-term WT1-DTH positivity after two vaccinations. Moreover, after 12 vaccinations, the percentages of both circulating regulatory T cells and myeloid-derived suppressor cells were significantly lower in patients with long-term WT1-DTH-positive PDAC than in short-term WT1-DTH-positive patients., Conclusions: Potent activation of WT1-specific immune responses through a combination chemoimmunotherapy regimen including the WT1-DC vaccine in patients with UR-PDAC may modulate the TME and enable conversion surgery, resulting in clinical benefits (Online supplemental file 1)., Trial Registration Number: jRCTc030190195., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: The need for mastering standard imaging techniques for convex EUS in the biliopancreatic regions has been increasing; however, large variations in the aptitude for achieving EUS competency hinder expert development. Therefore, we investigated the factors influencing the achievement of expert competency in EUS using a new assessment tool for multiple imaging items., Methods: Between January 2018 and February 2022, 3277 consecutive EUS procedures conducted by 5 beginners (EUS procedures <250), 7 intermediate trainees (250-749), and 2 experts (≥750) were prospectively evaluated. Immediately after each EUS procedure, the success or failure of imaging for each item was recorded using a newly developed EUS assessment tool that requires 17 items to be photographed. After correcting for missing values using multiple imputation, learning curves of EUS scores were created, and a competency was set based on expert scores. Finally, a comparative analysis between high and low performers was performed to extract factors influencing EUS scores., Results: Although 3 of 7 intermediates (43%; mean, 317 cases) achieved competency, none of the beginners achieved competency. During a comparative analysis, although no significant difference in the number of EUS procedures performed was observed between the high and low performers, the former had significantly higher scores in the written test (theoretical knowledge)., Conclusions: Our results showed that theoretical knowledge, rather than the number of EUS cases, may be a possible influencing factor for distinguishing high and low performers after treating 250 cases. (Clinical trial registration number: UMIN 000043271.)., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objectives: Selection criteria for self-expandable metal stents (SEMSs) with or without cover during palliative treatment of distal malignant biliary obstruction (DMBO) remain unclear. We evaluated factors associated with time to recurrent biliary obstruction (TRBO) in fully covered SEMSs (FCSEMSs) and uncovered SEMSs (UCSEMSs)., Methods: We retrospectively analyzed consecutive patients with DMBO who received a SEMS. TRBO was determined using the Kaplan-Meier analysis, and complications were compared between the FCSEMS and UCSEMS groups. After TRBO-associated factors were extracted using multivariate competing-risks regression (CRR), propensity score-adjusted CRRs were performed to verify their robustness., Results: There were 180 patients (66 FCSEMSs and 114 UCSEMSs) enrolled in this study. There was no significant difference between median TRBO in the FCSEMS and UCSEMS groups (275 vs. 255 days, p = 0.67). Complications were more frequent in the FCSEMS than UCSEMS group (21.2% vs. 8.8%; p = 0.023). Multivariate CRR for TRBO-associated factors revealed that "pancreatic ductal carcinoma (PDAC) treated with UCSEMS" was the only independent predictor of TRBO ( p = 0.03). Similarly, the propensity score-adjusted CRRs showed no significant difference in TRBO in "FCSEMS" vs "UCSEMS" ( p = 0.96); however, there was a significant difference in "PDAC using UCSEMS" vs "other" ( p = 0.043). In the palliative care group including any DMBO without chemotherapy, the first quartile of the TRBO of UCSEMS was 100 days., Conclusions: UCSEMSs are a possible option for both patients with DMBO arising from PDAC and for patients with any DMBO receiving palliative care who should avoid SEMS-related complications., Competing Interests: The author Kazuki Sumiyama is DEIC of DEN Open. The rest of the authors declare that they have no conflict of interest., (© 2022 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: The utility of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) alone in the biliopancreatic region appears to be limited because it is highly dependent on the experience and skill of the endoscopist. Therefore, the present study aimed to validate the efficacy of CH-EUS in clinical practice. Methods: Between January 2018 and March 2019, 301 consecutive patients who underwent CH-EUS were prospectively enrolled in this study. The diagnostic performance of CH-EUS was compared with that of dynamic computed tomography (CT), magnetic resonance imaging (MRI), and all combinations (i.e., CH-EUS, dynamic CT, and MRI) using a Bonferroni correction. A multiple logistic regression analysis was performed to extract each disease that allowed the CH-EUS diagnosis to be consistent with the final diagnosis. Results: In multiple comparisons of diagnostic performance, no significant differences were observed among dynamic CT, MRI, and CH-EUS (p = 1.00), but the diagnostic performance was significantly higher when all modalities were combined (p < 0.001). Moreover, only intraductal papillary mucinous neoplasm comprising adenoma or carcinoma (IPMN, n = 161) showed significance with respect to the agreement with the final diagnosis (p = 0.006). Conclusions: Our results showed that CH-EUS-based diagnosis of IPMN may be possible in clinical practice. On the contrary, to accurately diagnose biliopancreatic diseases other than IPMN, comprehensive diagnosis using multiple modalities may be necessary, rather than relying on CH-EUS alone.